The need for an accurate and non-invasive method for determining attributes of or analyte concentrations in bodily tissues, bodily fluids or other biological samples is well documented. For example, accurate non-invasive measurement of blood glucose levels in diabetic patients would greatly improve diabetes treatment. U.S. Pat. No. 5,379,764 to Barnes et al. discloses the necessity for diabetics to frequently monitor blood glucose levels. The more frequent the blood glucose levels are measured, the less likely the occurrence of large swings in blood glucose levels. These large swings are associated with the very undesirable short-term symptoms and long-term complications of diabetes. Such long-term complications include heart disease, arteriosclerosis, blindness, stroke, hypertension, kidney failure, and premature death.
Several systems have been proposed for the non-invasive measurement of blood glucose levels. However, despite these efforts, direct and invasive measurements (e.g., blood sampling by a lancet cut into the finger) are still necessary for most if not all presently FDA approved and commercially available glucose monitors. This is believed so compromising to the diabetic patient that frequent blood glucose measurement, which is necessary to ensure effective diabetes management, is rarely achieved.
It has been recognized that when the body is measured non-invasively, various parts of the body may be interrogated, such as the skin, the eye, the finger, etc. Also, depending on the non-invasive technique in question, different fluid compartments within the body may be measured. For example, European Patent No. 0 757 243 states that, “reflective arm measurements are limited to capillary blood (and interstitial fluid) almost exclusively”. Thennadil et al. (2001) also state that, “the glucose “seen” by the light consists of glucose in both the ISF and the capillary blood.” European Patent No. 0 631 137 states “the spectral information utilized by these methods includes not only that generated by glucose in the blood but also that from glucose in the interstitial fluid and other tissues.” Furthermore, International Publication No. WO 99/43255 reports that, “when light passes through the tongue it is believed that the majority of the photons will interact with interstitial fluid not blood.”
Since the advent of non-invasive blood glucose monitoring, many have reported using invasive finger capillary blood measurements as references, including Heise et al. in “Near-Infrared Reflectance Spectroscopy for Noninvasive Monitoring of Metabolites” (Clin. Chem. Lab. Med. 2000) and Ward et al. (1992). No distinction has been made about the best time to collect these reference measurements. Ward et al. actually reported using these references post-prandially, when the difference between capillary glucose and interstitial glucose can be expected to be at its greatest. Plasma glucose readings have also been used as calibration standards as stated by Gabriely et al. in “Transcutaneous Glucose Measurement Using Near-Infrared Spectroscopy During Hypoglycemia” (The American Diabetes Association, Inc., 1999), where the blood in question was venous blood. Venous readings are impractical outside of the process of calibration, for example, in cases where a home-user would make invasive measurements as a quality check or as part of a calibration model-updating scheme.
Using blood glucose as a reference for non-invasive measurements has been reported in published patent applications, such as International Publication No. WO 98/37805, where it is stated, “the patient's blood glucose is measured with a highly accurate invasive method which is relied upon to yield a reference measurement of the patient's blood glucose”. International Publication No. WO 01/16579 states that, “this individual calibration process requires taking a number of blood samples over a period of time from the individual, and obtaining reference glucose concentration measurements from these samples”, while International Publication No. WO 01/09589 reports that, “the glucose meter commercially available for diabetics' self use can be used to measure glucose concentration in the blood from a few microliters of capillary blood obtained, e.g., by lancing a finger.”
It is clear that while several researchers have acknowledged the fact that glucose kinetics result in differences between glucose in different compartments, there seems to be differing opinions on the extent to which the differences occur. For example, McGarraugh et al. in “Glucose Measurements Using Blood Extracted from the Forearm and the Finger” (Therasense White Paper, 2001) note that “changes in blood glucose are first detected in the finger sample and the changes lag in the arm measurements”, and that “glucose concentration from the arm never reaches as high a peak as the finger, nor does it experience as low a valley”. They concluded that, “the extremes in glucose readings from finger capillaries tend to be damped in capillary blood from the arm”
In addition, U.S. Pat. No. 6,049,727 to Crothall states that, “it is known that glucose levels in interstitial fluid lag glucose levels in blood by about 20 minutes.” Kuwa et al. in “Relationships of Glucose concentrations in Capillary Whole Blood, Venous Whole Blood and Venous Plasma” (Clin. Chim. Acta., 2001), also report that “post-loaded glucose values in capillary blood were significantly higher than those in venous blood”, and said that the reason for the difference was glucose consumption in the tissues. Meanwhile, McGuire et al. in “Effects of Arterial Versus Venous Sampling on Analysis of Glucose Kinetics in Man” (J. Appl. Phys., 1976) state that the reason for the difference in glucose concentration between arterial and venous blood was, “(1) the transit times of substances through the circulatory paths between the two sampling sites, and (2) the loss of substances to the intervening tissues”. On the other hand, International Publication No. WO 01/18543 states that, “although there is a time lag of a few minutes before changes in blood glucose concentration are reflected in the interstitial fluid, this lag is negligible compared to the usual time between measurements . . . measurement of interstitial fluid glucose may be an adequate surrogate for measurement of capillary blood glucose”. This opinion is also shared by Thennadil et al. (2001), who state, “no observable lag among ISF, and capillary and venous plasma glucose levels when blood glucose levels change rapidly”. This is contrary to International Publication No. WO 01/47408, whose authors have developed a “system for determining the level of glucose of a user, comprising a sampling device used to take a sample of interstitial fluid (ISF) and a means for reducing the time lag between the concentration of glucose in interstitial fluid and in the blood of the patient.” Thennadil et al. (2001), commenting on a non-invasive glucose calibration model generated using finger capillary blood glucose as a reference, say that, “any difference in glucose levels between the ISF and capillary blood will lead to a ‘reference’ error, which will depend on the relationship between blood and ISF glucose concentrations. If this ‘reference’ error is large, then the error in the non-invasive estimation of glucose will be dominated by it”. As mentioned above, however, they go on to conclude that there is, “no observable lag among ISF, and capillary and venous plasma glucose levels when blood glucose levels change rapidly.”